Single Ascending Dose Safety Study of BMS-962476 in Healthy Subjects and Patients With Elevated Cholesterol on Statins

Atherosclerosis Clinical Trial

Official title:

Randomized, Double-Blind, Placebo-Controlled, Ascending Single-Dose Study to Evaluate the Safety, Pharmacokinetics and Pharmacodynamics of BMS-962476 in Healthy Subjects and in Patients With Hypercholesterolemia on Statin Therapy

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01587365
• Other study ID #: CV206-001
• Status: Completed
• Phase: Phase 1
• First received: April 26, 2012
• Last updated: September 2, 2013
• Start date: May 2012
• Est. completion date: May 2013

Study information

• Verified date: September 2013
• Source: Bristol-Myers Squibb
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug AdministrationUnited States: Institutional Review Board
• Study type: Interventional

Clinical Trial Summary

To obtain safety and tolerability information in healthy subjects is administered as a single dose

Description:

• Study Classification: Pharmacokinetics and Pharmacodynamics

• Intervention Model: Single Ascending Dose (SAD) study

• Allocation: Randomized Non-Stratified

Recruitment information / eligibility

• Status: Completed
• Enrollment: 66
• Est. completion date: May 2013
• Est. primary completion date: May 2013
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 18 Years to 65 Years

Eligibility

Inclusion Criteria:

• Healthy population

• Untreated low density lipoprotein cholesterol (LDL-c) = 130 and = 190 mg/dL and triglycerides = 200 mg/dL

• Body Mass Index (BMI) of 18 to 35 kg/m2 inclusive

• Men and women, ages 18 to 65 years, inclusive

• Statin population

• Patients with hypercholesterolemia on stable statin therapy for 6 weeks prior to enrollment

• At enrollment, LDL-c = 100mg/dL and triglycerides = 200 mg/dL

• Patients with controlled hypertension on a stable dose of no more than two antihypertensive drugs

• BMI of 18 to 37 kg/m2 inclusive

• Men and women, ages 18 to 75 years inclusive

Exclusion Criteria:

• Healthy Population

• Subjects with fasting LDL-c < 130 or > 190 mg/dL, or fasting triglycerides > 200 mg/dL

• Subjects at increased 10-year cardiovascular risk of = 20% based on Framingham risk score

• Subjects with any significant acute or chronic medical illness at the time of screening, including history of cancer, known history of sickle cell disease or trait, and known history of thalassemia

• Statin population

• Patients with fasting LDL-c < 100mg/dL, or fasting triglycerides > 200 mg/dL on statin therapy

• Patients on prescription or over the counter lipid-lowering therapy other than statin therapy

• Patients with established atherosclerotic vascular disease

• Patients with diabetes who are requiring oral or injectable anti-diabetic drug therapy

• Patients with uncontrolled hypertension or controlled hypertension requiring more than two antihypertensive drugs

• Patients with any significant acute or chronic medical illness that is severe, progressive or uncontrolled at the time of screening

• Use of any lipid lowering medication including over the counter products (eg, niacin > 500 mg; omega-3 fatty acids > 1000 mg; red rice yeast; phytosterols or stanol esters) for lipid lowering within 30 days prior to screening visit (42 days for fibrates) with the exception of stable statin therapy in the target disease population

• Prior treatment with any monoclonal antibody or investigational protein biologic within the preceding one year before study drug administration

• Concurrent or use within 3 months of study drug administration of marketed or investigational systemic or inhaled corticosteroids or other immunosuppressant drugs, and within 6 weeks for topical corticosteroids

Study Design

Allocation: Randomized, Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Atherosclerosis

Intervention

Biological:
• BMS-962476

• Placebo matching with BMS-962476

Locations

Country	Name	City	State
United States	Metabolic And Atherosclerosis Research Center/ Medpace Clinical Pharmacology	Cincinnati	Ohio

Sponsors (1)

Lead Sponsor	Collaborator
Bristol-Myers Squibb

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Safety and tolerability of BMS-962476 as measured by the number of subjects with serious adverse events, deaths or discontinuations due to adverse events (AEs), AEs of injection site reactions, or potentially clinically significant changes in vital signs		Up to Day 43	Yes
Secondary	Pharmacodynamic effects of single subcutaneous (SC) and intravenous (IV) doses of BMS-962476	Pharmacodynamic effects will be measured by fasting lipid panel	Up to Day 43	No
Secondary	Maximum observed plasma concentration (Cmax) of single dose pharmacokinetics (PK) and dose proportionality of BMS-962476 following SC and IV administration		17 time points up to Day 43	No
Secondary	Time of maximum observed plasma concentration (Tmax) of single dose pharmacokinetics (PK) and dose proportionality of BMS-962476 following SC and IV administration		17 time points up to Day 43	No
Secondary	Area under the plasma concentration-time curve from time zero to the time of last quantifiable plasma concentration [AUC(0-T)] of single dose pharmacokinetics (PK) and dose proportionality of BMS-962476 following SC and IV administration		17 time points up to Day 43	No
Secondary	Area under the plasma concentration-time curve from time zero extrapolated to infinite time [AUC(INF)] of single dose pharmacokinetics (PK) and dose proportionality of BMS-962476 following SC and IV administration		17 time points up to Day 43	No
Secondary	Plasma elimination half-life (T-HALF) of single dose pharmacokinetics (PK) and dose proportionality of BMS-962476 following SC and IV administration		17 time points up to Day 43	No
Secondary	Total body clearance (CL/F) of BMS-962476 SC Dosing		15 time points up to Day 43	No
Secondary	Total body clearance (CL) of BMS-962476 IV Dosing		17 time points up to Day 43	No
Secondary	Volume of distribution at steady state (Vss/F) of BMS-962476 SC Dosing		15 time points up to Day 43	No
Secondary	Volume of distribution at steady state (Vss) of BMS-962476 IV Dosing		15 time points up to Day 43	No
Secondary	Absolute bioavailability (F) of total and free BMS-962476		15 time points up to Day 43	No
Secondary	Frequency of anti-BMS-962476 antibodies (immunogenicity) following single SC and IV doses of BMS-962476		Up to Day 43	Yes

External Links

•   BMS clinical trial educational resource
•   BMS Clinical Trial Information
•   For FDA Safety Alerts and Recalls refer to the following link: http://www.fda.gov/MEDWATCH/safety.htm
•   Investigator Inquiry form